■在肾功能良好的中年人中,载脂蛋白L1(APOL1)基因型对未来肾病风险的影响尚不明确。
■纵向队列研究。
■总共,5,886名健康个体(45-64岁)参加了社区动脉粥样硬化风险研究,其基于肌酐的估计肾小球滤过率≥80mL/min,将是合适的肾脏供体。
■种族和APOL1基因型。
■使用CKD-EPI(慢性肾脏病流行病学合作)2021方程,基于肌动蛋白和胱抑素C的估计肾小球滤过率(eGFRcr-cys),尿白蛋白-肌酐比值(UACR),慢性肾脏病(CKD)3a或更严重的比例,终末期肾病(ESKD),和死亡。
■参与者根据种族和APOL1基因型进行分组。各组比较eGFRcr-cys和UACR。使用多项逻辑回归模型比较CKD的几率。建立Kaplan-Meier存活曲线以比较最后随访时的ESKD和死亡率。
■有5,075名白人(86%),701携带低风险APOL1基因型的黑人(12%),和110名携带高风险APOL1基因型的黑人(2%)。基线时的平均年龄为53±6岁。十年后,白人参与者的eGFRcr-cys低于低危和高危人群(分别为89±16vs91±16和92±15mL/min/1.73m2;P<0.001)。25岁时,白人参与者的eGFRcr-cys继续低于低风险组(70±18vs72±19mL/min/1.73m2;P<0.001),但与高风险APOL1基因型(67±23mL/min/1.73m2)相比没有。在10岁和25岁时,各组之间的UACR没有差异(分别为P=0.87和0.91)。在未调整模型和调整模型中,低风险和高风险APOL1组发生CKD3a期或更差的几率没有差异(分别为P=0.26和P=0.39)。在最后的随访中,<5%发达的ESKD,45%的个体死亡或达到ESKD,组间结局无差异.
■由于死亡和长期随访而导致的确定性低。
■在中年人中,APOL1基因型似乎不是未来肾病风险的主要驱动因素。
患有肾病的黑人患者携带2种载脂蛋白L1(APOL1)基因变体,被称为高风险基因型,与具有0或1个风险变异的患者相比,肾功能加速下降。尚不清楚高危基因型是否会对健康中年人的肾功能产生负面影响。我们评估了APOL1基因型对基线时肾功能和血压正常的社区动脉粥样硬化风险研究参与者(平均年龄53岁)的肾功能的影响。在25年的随访中,APOL1高危基因型似乎不是未来肾病风险的主要驱动因素.我们的研究结果与老年活体捐献者以及APOL1相关肾脏疾病患者的家庭成员的咨询有关。
UNASSIGNED: The effect of apolipoprotein L1(APOL1) genotype on future risk of kidney disease among middle-aged individuals with good kidney function is not well established.
UNASSIGNED: Longitudinal cohort study.
UNASSIGNED: In total, 5,886
healthy individuals (45-64 years old) enrolled in the Atherosclerosis Risk in Communities study with creatinine-based estimated glomerular filtration rate ≥ 80 mL/min who would be suitable kidney donors.
UNASSIGNED: Race and APOL1 genotype.
UNASSIGNED: Creatinine- and cystatin C-based estimated glomerular filtration rate (eGFRcr-cys) using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) 2021 equation, urinary albumin-creatinine ratio (UACR), proportion with chronic kidney disease (CKD) 3a or worse, end-stage kidney disease (ESKD), and death.
UNASSIGNED: Participants grouped based on race and APOL1 genotype. Compared eGFRcr-cys and UACR across groups. Multinomial logistic regression models were used compare odds of CKD. Kaplan-Meier survival curves were created to compare rates of ESKD and death at last follow-up.
UNASSIGNED: There were 5,075 Whites (86%), 701 Blacks carrying the low-risk APOL1 genotype (12%), and 110 Blacks carrying the high-risk APOL1 genotype (2%). The mean age at baseline was 53 ± 6 years. At 10 years, White participants had lower eGFRcr-cys than low-risk and high-risk groups (89 ± 16 vs 91 ± 16 and 92 ± 15 mL/min/1.73 m2, respectively; P < 0.001). At 25 years, White participants continued to have lower eGFRcr-cys than the low-risk group (70 ± 18 vs 72 ± 19 mL/min/1.73 m2; P < 0.001) but not compared with the high-risk APOL1 genotype (67±23 mL/min/1.73 m2). There was no difference in UACR among groups at 10 and 25 years (P = 0.87 and 0.91, respectively). The odds of developing CKD stage 3a or worse were not different between low-risk and high-risk APOL1 group in both unadjusted and adjusted models (P = 0.26 and P = 0.39, respectively). At last follow-up, <5% developed ESKD, and 45% of individuals either died or reached ESKD with no difference in outcomes between the groups.
UNASSIGNED: Low ascertainment because of death and long follow-up.
UNASSIGNED: Among middle-aged individuals, APOL1 genotype does not appear to be a major driver of future risk of kidney disease.
Black patients with kidney disease carrying 2 variants of the apolipoprotein L1 (APOL1) gene, referred to as the high-risk genotype, experience an accelerated decline in kidney function than those with 0 or 1 risk variant. It is unknown whether the high-risk genotype negatively affects kidney function of
healthy middle-aged individuals. We evaluated the effect of APOL1 genotype on kidney function of the Atherosclerosis Risk in Communities study participants (mean age 53 years) who had normal kidney function and blood pressure at baseline. At 25 years of follow-up, the APOL1 high-risk genotype did not appear to be a major driver of future risk of kidney disease. Our study findings are relevant for counseling older living donor candidates as well as family members of patients with APOL1-associated kidney disease.